Proceedings of the National Academy of Sciences of the United States of America

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• Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy AI翻译
  作者：Huijbers, Elisabeth J. M.; van Beijnum, Judy R.; van Loon, Karlijn; Griffioen, Christian J.; Volckmann, Richard; Bassez, Ayse; Lambrechts, Diether; Monteiro, Madalena Nunes; Jimenez, Connie R.; Hogendoorn, Pancras C. W.; Koster, Jan; Griffioen, Arjan W.
  作者单位：University of Amsterdam; Vrije Universiteit Amsterdam; University of Amsterdam; Vrije Universiteit Amsterdam; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Amsterdam; University of Amsterdam; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC)
  摘要：A sustained blood supply is critical for tumor growth, as it delivers the nutrients and oxygen required for development. Targeting of blood vessel formation via immunotherapies is an area of great importance. Knowing that certain embryonic genes, such as carcinoembryonic antigens (CEA) and oncofetal fibronectin, become reexpressed in malignant transformation, we hypothesized that a similar phenomenon holds true for tumor endothelial cells (TECs) as well. An approach for identification of highl...
• Spiral spin liquid noise AI翻译
  作者：Takahashi, Hiroto; Hsu, Chun-Chih-Chih; Jerzembeck, Fabian; Murphy, Jack; Ward, Jonathan; Enright, Jack D.; Knapp, Jan; Puphal, Pascal; Isobe, Masahiko; Matsumoto, Yosuke; Takagi, Hidenori; Davis, J. C. Seamus; Blundell, Stephen J.
  作者单位：University of Oxford; Max Planck Society; University College Cork; Max Planck Society; Cornell University
  摘要：An emerging concept for identification of different types of spin liquids [C. Broholm et al., Science 367, eaay0668 (2020)] is through the use of spontaneous spin noise [S. Chatterjee, J. F. Rodriguez-Nieva, E. Demler, Phys. Rev. B 99, 104425 (2019)]. Here, we develop spin noise spectroscopy for spin liquid studies by considering Ca10Cr7O28, a material hypothesized to be either a quantum or a spiral spin liquid (SSL). By enhancing techniques introduced for magnetic monopole noise studies [R. D...
• MITD1 is a brain- specific interferon- inducible factor that inhibits flavivirus replication AI翻译
  作者：Zoladek, Jim; Cannac, Marion; Seite, Mael; Davies, Emma; Quellec, Jordan; Barthelemy, Jonathan; Gorna, Kamila; Desgraupes, Sophie; Bribes, Ines; Salinas, Sara; Coulpier, Muriel; Arhel, Nathalie J.; Palmarini, Massimo; Simonin, Yannick; Wilson, Sam J.; Nisole, Sebastien
  作者单位：Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Glasgow; INRAE; Universite de Montpellier; CIRAD; Agence Nationale de Securite Sanitaire de l'Alimentation, de l'Environnement du Travail (ANSES); Laboratoire de Sante Animale de Maisons-Alfort; INRAE; Ecole Nationale Veterinaire d'Alfort (ENVA); University of Cambridge
  摘要：West Nile virus (WNV) and Usutu virus (USUV) are closely related mosquito- borne neurotropic flaviviruses that share common transmission cycle and can infect humans. However, while human infections by WNV are widespread, infections by USUV are comparatively less frequent, less severe, and currently limited to Africa and Europe. To identify human host factors that contribute to the pathogenic signatures of these two flaviviruses, we carried out an arrayed expression screen of over 1,300 interfe...
• Variable DPP4 expression in multiciliated cells of the human nasal epithelium as a determinant for MERS-CoV tropism AI翻译
  作者：Breugem, Tim I.; Riesebosch, Samra; Zhang, Jingshu; Mykytyn, Anna Z.; Krabbendam, Lisette; Groen, Nathalie; Varela, Sivana Baptista; Schipper, Debby; Doel, Petra B. van den; van Acker, Romy; Stadhouders, Ralph; Lamers, Mart M.; Haagmans, Bart L.
  作者单位：Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; National University of Singapore; University of Amsterdam
  摘要：Transmissibility of respiratory viruses is a complex viral trait that is intricately linked to tropism. Several highly transmissible viruses, including severe acute respiratory syndrome coronavirus 2 and Influenza viruses, specifically target multiciliated cells in the upper respiratory tract to facilitate efficient human- to- human transmission. In contrast, the zoonotic Middle East respiratory syndrome coronavirus (MERS- CoV) generally transmits poorly between humans, which is largely attrib...
• Results from the inSight Mars mission do not require a water- saturated mid crust AI翻译
  作者：Jakosky, Bruce M.
  作者单位：University of Colorado System; University of Colorado Boulder
• Epitope-directed selection of GPCR nanobody ligands with evolvable function AI翻译
  作者：Skiba, Meredith A.; Canavan, Clare; Nemeth, Genevieve R.; Liu, Jinghan; Kanso, Ali; Kruse, Andrew C.
  作者单位：Harvard University; Harvard Medical School; Northwestern University; Leipzig University
  摘要：Antibodies have the potential to target G protein-coupled receptors (GPCRs) with high receptor, cellular, and tissue selectivity; however, few antibody ligands for GPCRs exist. Here, we describe a generalizable selection method to enrich for GPCR ligands from a synthetic camelid antibody fragment (nanobody) library. Our strategy yielded multiple nanobody ligands for the angiotensin II type I receptor (AT1R), a prototypical GPCR and important drug target. We found that nanobodies readily act as...
• Insulation between adjacent TADs is controlled by the width of their boundaries through distinct mechanisms AI翻译
  作者：Papale, Andrea; Segueni, Julie; Elmaroufi, Hanae; Noordermeer, Daan; Holcman, David
  作者单位：Universite PSL; Ecole Normale Superieure (ENS); CEA; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); University of Cambridge
  摘要：Topologically associating domains (TADs) are sub-Megabase regions in vertebrate genomes with enriched intradomain interactions that restrict enhancer-promoter contacts across their boundaries. However, the mechanisms that separate TADs remain incompletely understood. Most boundaries between TADs contain CTCF binding sites (CBSs), which individually contribute to the blocking of Cohesin-mediated loop extrusion. Using genome-wide classification, here we show that the width of TAD boundaries form...
• NOTCH, ERK, and SHH signaling respectively control the fate determination of cortical glia and olfactory bulb interneurons AI翻译
  作者：Gao, Yanjing; Sun, Mengge; Fu, Tongye; Wang, Ziwu; Jiang, Xin; Yang, Lin; Liang, Xiaoyi G.; Liu, Guoping; Tian, Yu; Yang, Feihong; Li, Jialin; Li, Zhenmeiyu; Li, Xiaosu; You, Yan; Ding, Chaoqiong; Wang, Yuan; Ma, Tong; Zhang, Zhuangzhi; Xu, Zhejun; Chen, Bin; Yang, Zhengang
  作者单位：Fudan University; Fudan University; University of California System; University of California Santa Cruz; Sichuan University
  摘要：During cortical development, radial glial cells (neural stem cells) initially are neurogenic, generating intermediate progenitor cells that exclusively produce glutamatergic pyramidal neurons. Next, radial glial cells generate tripotential intermediate progenitor cells (Tri-IPCs) that give rise to cortical astrocytes and oligodendrocytes, and olfactory bulb interneurons. The molecular mechanisms underlying the transition from cortical neurogenesis to gliogenesis, and the subsequent fate determ...
• Robust encoding of stimulus-response mapping by neurons in visual cortex AI翻译
  作者：Jonikaitis, Donatas; Xia, Ruobing; Moore, Tirin
  作者单位：Stanford University; Howard Hughes Medical Institute; Stanford University
  摘要：Neural activity in sensory cortex is modulated by behavioral and cognitive factors, and this modulation is thought to contribute to the selection of specific sensory information needed to achieve behavioral goals. In contrast, more abstract behavioral variables that are independent of stimulus selection, such as stimulus-response mapping, are thought to be encoded by neurons outside of sensory cortex. We show that information about such mapping is robustly encoded in the responses of neurons i...
• Thiopurine therapy enhances immune checkpoint inhibitor efficacy in low- mutational burden melanoma: A promising anticancer approach AI翻译
  作者：Nazerai, Loulieta; Tsiavou, Christina; Vardouli, Lina; Schmiegelow, Kjeld; De Zio, Daniela
  作者单位：Rigshospitalet; University of Copenhagen; University of Copenhagen; University of Southern Denmark
  摘要：A key limitation of immune checkpoint inhibitors (ICI) therapy is their reduced efficacy toward cancers with a low tumor mutational burden (TMB). Since low- TMB tumors express fewer neoantigens, they are less responsive to ICI therapy like anti- PD- 1 and anti- CTLA- 4. In preclinical immunocompetent mouse models of low- TMB melanoma, we recently demonstrated that exposure to 6- thioguanine (6TG) significantly improved tumor control by increasing TMB and creating a proinflammatory tumor microe...